ArticleCell death & disease2020
Enalapril overcomes chemoresistance and potentiates antitumor efficacy of 5-FU in colorectal cancer by suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 77 citations in OpenAlex.
- The intersection of colorectal cancer and cardiovascular disease: shared mechanisms and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Chemotherapeutic Potential of Fluorouracil-Platinum (IV) Prodrugs Against Cisplatin-Resistant Colorectal Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- TBKBP1 induces capecitabine resistance through negative regulation of type I interferon pathway in triple-negative breast cancer.Oncogene · 2026Article
- Computational Elucidation of Hub Genes and Pathways Correlated with the Development of 5-Fluorouracil Resistance in HCT 116 Colorectal Carcinoma Cell Line.Biochemical genetics · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Innovative horizons: harnessing drug repositioning for targeted therapeutics in colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer.Cancer cell international · 2025Review
- Targeting the NF-κB Pathway in Cancer: Mechanisms, Resistance, and Therapeutic Potential Across Tumor Types.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2025Review
- The Multifaceted Roles of Neutrophil Death in COPD and Lung Cancer.Journal of respiratory biology and translational medicine · 2025Article
- Bcl‑xL‑specific BH3 mimetic A‑1331852 suppresses proliferation of fluorouracil‑resistant colorectal cancer cells by inducing apoptosis.Oncology reports · 2025Article
- Understanding microRNA-Mediated Chemoresistance in Colorectal Cancer Treatment.International journal of molecular sciences · 2025Review
- Postdiagnostic use of antihypertensive medications and survival in colorectal, lung, corpus uteri, melanoma and kidney cancer patients with hypertension.BMC cancer · 2025Article
- Microbiome-mediated regulation of chemoradiotherapy response.Frontiers in oncology · 2025Review
- Correlation Between Antihypertensive Drugs and Survival Among Patients with Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Versatile function of NF-ĸB in inflammation and cancer.Experimental hematology & oncology · 2024Review
- Innovative Strategies to Combat 5-Fluorouracil Resistance in Colorectal Cancer: The Role of Phytochemicals and Extracellular Vesicles.International journal of molecular sciences · 2024Review
- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU) is one of the most effective drugs for the treatment of colorectal cancer (CRC). However, there is an urgent need in reducing its systemic side effects and chemoresistance to make 5-FU-based chemotherapy more effective and less toxic in the treatment of CRC. Here, enalapril, a clinically widely used antihypertensive and anti-heart failure drug, has been verified as a chemosensitizer that extremely improves the sensitivity of CRC cells to 5-FU. Enalapril greatly augmented the cytotoxicity of 5-FU on the cell growth in both established and primary CRC cells. The combination of enalapril and 5-FU synergistically suppressed the cell migration and invasion in both 5-FU-sensitive and -resistant CRC cells in vitro, and inhibited angiogenesis, tumor growth, and metastasis of 5-FU-resistant CRC cells in vivo without increased systemic toxicity at concentrations that were ineffective as individual agents. Furthermore, combined treatment cooperatively inhibited NF-κB/STAT3 signaling pathway and subsequently reduced the expression levels of NF-κB/STAT3-regulated proteins (c-Myc, Cyclin D1, MMP-9, MMP-2, VEGF, Bcl-2, and XIAP) in vitro and in vivo. This study provides the first evidence that enalapril greatly sensitized CRC cells to 5-FU at clinically achievable concentrations without additional toxicity and the synergistic effect may be mainly by cooperatively suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.